Product Elements:
Ursodiol ursodiol ursodiol ursodiol starch, corn silicon dioxide magnesium stearate d&c red no. 28 d&c yellow no. 10 fd&c blue no. 1 fd&c blue no. 2 fd&c red no. 40 gelatin, unspecified ferrosoferric oxide titanium dioxide pink opaque white e503
Indications and Usage:
Indications and usage ⢠ursodiol is indicated for patients with radiolucent, noncalcified gallbladder stones < 20 mm in greatest diameter in whom elective cholecystectomy would be undertaken except for the presence of increased surgical risk due to systemic disease, advanced age, idiosyncratic reaction to general anesthesia, or for those patients who refuse surgery. safety of use of ursodiol beyond 24 months is not established. ⢠ursodiol is indicated for the prevention of gallstone formation in obese patients experiencing rapid weight loss.
Dosage and Administration:
Dosage and administration gallstone dissolution the recommended dose for ursodiol treatment of radiolucent gallbladder stones is 8 - 10 mg/kg/day given in 2 or 3 divided doses. ultrasound images of the gallbladder should be obtained at 6-month intervals for the first year of ursodiol therapy to monitor gallstone response. if gallstones appear to have dissolved, ursodiol therapy should be continued and dissolution confirmed on a repeat ultrasound examination within 1 to 3 months. most patients who eventually achieve complete stone dissolution will show partial or complete dissolution at the first on-treatment reevaluation. if partial stone dissolution is not seen by 12 months of ursodiol therapy, the likelihood of success is greatly reduced. gallstone prevention the recommended dosage of ursodiol for gallstone prevention in patients undergoing rapid weight loss is 600 mg/day (300 mg b.i.d.).
Contraindications:
Contraindications ⢠ursodiol will not dissolve calcified cholesterol stones, radiopaque stones, or radiolucent bile pigment stones. hence, patients with such stones are not candidates for ursodiol therapy. ⢠patients with compelling reasons for cholecystectomy including unremitting acute cholecystitis, cholangitis, biliary obstruction, gallstone pancreatitis, or biliary-gastrointestinal fistula are not candidates for ursodiol therapy. ⢠allergy to bile acids.
Adverse Reactions:
Adverse reactions the nature and frequency of adverse experiences were similar across all groups. the following tables provide comprehensive listings of the adverse experiences reported that occurred with a 5% incidence level: gallstone dissolution ursodiol 8 - 10 mg/kg/day (n=155) placebo (n=159) n (%) n (%) body as a whole allergy 8 (5.2) 7 (4.4) chest pain 5 (3.2) 10 (6.3) fatigue 7 (4.5) 8 (5.0) infection viral 30 (19.4) 41 (25.8) digestive system abdominal pain 67 (43.2) 70 (44.0) cholecystitis 8 (5.2) 7 (4.4) constipation 15 (9.7) 14 (8.8) diarrhea 42 (27.1) 34 (21.4) dyspepsia 26 (16.8) 18 (11.3) flatulence 12 (7.7) 12 (7.5) gastrointestinal disorder 6 (3.9) 8 (5.0) nausea 22 (14.2) 27 (17.0) vomiting 15 (9.7) 11 (6.9) musculoskeletal system arthralgia 12 (7.7) 24 (15.1) arthritis 9 (5.8) 4 (2.5) back pain 11 (7.1) 18 (11.3) myalgia 9 (5.8) 9 (5.7) nervous system headache 28 (18.1) 34 (21.4) insomnia 3 (1.9) 8 (5.0) respiratory system bronchitis 10 (6.5) 6 (3.8) coughing 11 (7.1
Read more...) 7 (4.4) pharyngitis 13 (8.4) 5 (3.1) rhinitis 8 (5.2) 11 (6.9) sinusitis 17 (11.0) 18 (11.3) upper respiratory tract infection 24 (15.5) 21 (13.2) urogenital system urinary tract infection 10 (6.5) 7 (4.4) gallstone prevention ursodiol 600 mg (n=322) placebo (n=325) n (%) n (%) body as a whole fatigue 25 (7.8) 33 (10.2) infection viral 29 (9.0) 29 (8.9) influenza-like symptoms 21 (6.5) 19 (5.8) digestive system abdominal pain 20 (6.2) 39 (12.0) constipation 85 (26.4) 72 (22.2) diarrhea 81 (25.2) 68 (20.9) flatulence 15 (4.7) 24 (7.4) nausea 56 (17.4) 43 (13.2) vomiting 44 (13.7) 44 (13.5) musculoskeletal system back pain 38 (11.8) 21 (6.5) musculoskeletal pain 19 (5.9) 15 (4.6) nervous system dizziness 53 (16.5) 42 (12.9) headache 80 (24.8) 78 (24.0) respiratory system pharyngitis 10 (3.1) 19 (5.8) sinusitis 17 (5.3) 18 (5.5) upper respiratory tract infection 40 (12.4) 35 (10.8) skin and appendages alopecia 17 (5.3) 8 (2.5) urogenital system dysmenorrhea 18 (5.6) 19 (5.8)
Adverse Reactions Table:
| GALLSTONE DISSOLUTION |
| Ursodiol8 - 10 mg/kg/day(N=155) | Placebo(N=159) |
| N | (%) | N | (%) |
| Body as a Whole | | | | |
| Allergy | 8 | (5.2) | 7 | (4.4) |
| Chest Pain | 5 | (3.2) | 10 | (6.3) |
| Fatigue | 7 | (4.5) | 8 | (5.0) |
| Infection Viral | 30 | (19.4) | 41 | (25.8) |
| Digestive System | | | | |
| Abdominal Pain | 67 | (43.2) | 70 | (44.0) |
| Cholecystitis | 8 | (5.2) | 7 | (4.4) |
| Constipation | 15 | (9.7) | 14 | (8.8) |
| Diarrhea | 42 | (27.1) | 34 | (21.4) |
| Dyspepsia | 26 | (16.8) | 18 | (11.3) |
| Flatulence | 12 | (7.7) | 12 | (7.5) |
| Gastrointestinal Disorder | 6 | (3.9) | 8 | (5.0) |
| Nausea | 22 | (14.2) | 27 | (17.0) |
| Vomiting | 15 | (9.7) | 11 | (6.9) |
| Musculoskeletal System | | | | |
| Arthralgia | 12 | (7.7) | 24 | (15.1) |
| Arthritis | 9 | (5.8) | 4 | (2.5) |
| Back Pain | 11 | (7.1) | 18 | (11.3) |
| Myalgia | 9 | (5.8) | 9 | (5.7) |
| Nervous System | | | | |
| Headache | 28 | (18.1) | 34 | (21.4) |
| Insomnia | 3 | (1.9) | 8 | (5.0) |
| Respiratory System | | | | |
| Bronchitis | 10 | (6.5) | 6 | (3.8) |
| Coughing | 11 | (7.1) | 7 | (4.4) |
| Pharyngitis | 13 | (8.4) | 5 | (3.1) |
| Rhinitis | 8 | (5.2) | 11 | (6.9) |
| Sinusitis | 17 | (11.0) | 18 | (11.3) |
| Upper Respiratory Tract Infection | 24 | (15.5) | 21 | (13.2) |
| Urogenital System | | | | |
| Urinary Tract Infection | 10 | (6.5) | 7 | (4.4) |
| GALLSTONE PREVENTION |
| Ursodiol600 mg(N=322) | Placebo(N=325) |
| N | (%) | N | (%) |
| Body as a Whole | | | | |
| Fatigue | 25 | (7.8) | 33 | (10.2) |
| Infection Viral | 29 | (9.0) | 29 | (8.9) |
| Influenza-like Symptoms | 21 | (6.5) | 19 | (5.8) |
| Digestive System | | | | |
| Abdominal Pain | 20 | (6.2) | 39 | (12.0) |
| Constipation | 85 | (26.4) | 72 | (22.2) |
| Diarrhea | 81 | (25.2) | 68 | (20.9) |
| Flatulence | 15 | (4.7) | 24 | (7.4) |
| Nausea | 56 | (17.4) | 43 | (13.2) |
| Vomiting | 44 | (13.7) | 44 | (13.5) |
| Musculoskeletal System | | | | |
| Back Pain | 38 | (11.8) | 21 | (6.5) |
| Musculoskeletal Pain | 19 | (5.9) | 15 | (4.6) |
| Nervous System | | | | |
| Dizziness | 53 | (16.5) | 42 | (12.9) |
| Headache | 80 | (24.8) | 78 | (24.0) |
| Respiratory System | | | | |
| Pharyngitis | 10 | (3.1) | 19 | (5.8) |
| Sinusitis | 17 | (5.3) | 18 | (5.5) |
| Upper Respiratory Tract Infection | 40 | (12.4) | 35 | (10.8) |
| Skin and Appendages | | | | |
| Alopecia | 17 | (5.3) | 8 | (2.5) |
| Urogenital System | | | | |
| Dysmenorrhea | 18 | (5.6) | 19 | (5.8) |
Overdosage:
Overdosage neither accidental nor intentional overdosing with ursodiol has been reported. doses of ursodiol in the range of 16 - 20 mg/kg/day have been tolerated for 6 - 37 months without symptoms by 7 patients. the ld 50 for ursodiol in rats is over 5000 mg/kg given over 7 - 10 days and over 7500 mg/kg for mice. the most likely manifestation of severe overdose with ursodiol would probably be diarrhea, which should be treated symptomatically.
Description:
Description ursodiol is a bile acid available as 300 mg capsules suitable for oral administration. ursodiol, usp (ursodeoxycholic acid), is a naturally occurring bile acid found in small quantities in normal human bile and in the biles of certain other mammals. it is a bitter-tasting, white powder freely soluble in ethanol, methanol, and glacial acetic acid; sparingly soluble in chloroform; slightly soluble in ether; and insoluble in water. the chemical name for ursodiol is 3α, 7β-dihydroxy-5β-cholan-24-oic acid (c 24 h 40 o 4 ). ursodiol, usp has a molecular weight of 392.57. its structure is shown below: inactive ingredients: corn starch, magnesium stearate, silicon dioxide and the capsule shell contain the following ingredients, gelatin, titanium dioxide, d&c red # 28, fd&c blue # 1 and fd&c red # 40. the imprinting ink contains the following: black iron oxide, d&c yellow # 10 aluminum lake, fd&c blue # 1 aluminum lake, fd&c blue # 2 aluminum lake, fd&c red # 40 aluminum lake, propylene glycol and shellac glaze. structural-formula
Clinical Pharmacology:
Clinical pharmacology about 90% of a therapeutic dose of ursodiol is absorbed in the small bowel after oral administration. after absorption, ursodiol enters the portal vein and undergoes efficient extraction from portal blood by the liver (i.e., there is a large âfirst-passâ effect) where it is conjugated with either glycine or taurine and is then secreted into the hepatic bile ducts. ursodiol in bile is concentrated in the gallbladder and expelled into the duodenum in gallbladder bile via the cystic and common ducts by gallbladder contractions provoked by physiologic responses to eating. only small quantities of ursodiol appear in the systemic circulation and very small amounts are excreted into urine. the sites of the drugâs therapeutic actions are in the liver, bile, and gut lumen. beyond conjugation, ursodiol is not altered or catabolized appreciably by the liver or intestinal mucosa. a small proportion of orally administered drug undergoes bacterial degradation wit
Read more...h each cycle of enterohepatic circulation. ursodiol can be both oxidized and reduced at the 7-carbon, yielding either 7-keto-lithocholic acid or lithocholic acid, respectively. further, there is some bacterially catalyzed deconjugation of glyco- and tauro-ursodeoxycholic acid in the small bowel. free ursodiol, 7-keto-lithocholic acid, and lithocholic acid are relatively insoluble in aqueous media and larger proportions of these compounds are lost from the distal gut into the feces. reabsorbed free ursodiol is reconjugated by the liver. eighty percent of lithocholic acid formed in the small bowel is excreted in the feces, but the 20% that is absorbed is sulfated at the 3-hydroxyl group in the liver to relatively insoluble lithocholyl conjugates which are excreted into bile and lost in feces. absorbed 7-keto-lithocholic acid is stereospecifically reduced in the liver to chenodiol. lithocholic acid causes cholestatic liver injury and can cause death from liver failure in certain species unable to form sulfate conjugates. lithocholic acid is formed by 7-dehydroxylation of the dihydroxy bile acids (ursodiol and chenodiol) in the gut lumen. the 7-dehydroxylation reaction appears to be alpha-specific, i.e., chenodiol is more efficiently 7-dehydroxylated than ursodiol and, for equimolar doses of ursodiol and chenodiol, levels of lithocholic acid appearing in bile are lower with the former. man has the capacity to sulfate lithocholic acid. although liver injury has not been associated with ursodiol therapy, a reduced capacity to sulfate may exist in some individuals, but such a deficiency has not yet been clearly demonstrated.
Pharmacodynamics:
Pharmacodynamics ursodiol suppresses hepatic synthesis and secretion of cholesterol, and also inhibits intestinal absorption of cholesterol. it appears to have little inhibitory effect on synthesis and secretion into bile of endogenous bile acids, and does not appear to affect secretion of phospholipids into bile. with repeated dosing, bile ursodeoxycholic acid concentrations reach a steady state in about 3 weeks. although insoluble in aqueous media, cholesterol can be solubilized in at least two different ways in the presence of dihydroxy bile acids. in addition to solubilizing cholesterol in micelles, ursodiol acts by an apparently unique mechanism to cause dispersion of cholesterol as liquid crystals in aqueous media. thus, even though administration of high doses (e.g., 15 - 18 mg/kg/day) does not result in a concentration of ursodiol higher than 60% of the total bile acid pool, ursodiol-rich bile effectively solubilizes cholesterol. the overall effect of ursodiol is to increase the concentration level at which saturation of cholesterol occurs. the various actions of ursodiol combine to change the bile of patients with gallstones from cholesterol-precipitating to cholesterol-solubilizing, thus resulting in bile conducive to cholesterol stone dissolution. after ursodiol dosing is stopped, the concentration of the bile acid in bile falls exponentially, declining to about 5% - 10% of its steady state level in about 1 week.
How Supplied:
How supplied ursodiol capsules usp, 300 mg are #0 capsules with a pink opaque cap, white opaque body, imprinted âÐ503â in black ink on cap and body, filled with white powder. it is supplied in: carton of 50 capsules (10 capsules each blister pack x 5), ndc 0904-6221-06 carton of 100 capsules (10 capsules each blister pack x 10), ndc 0904-6221-61 store at 20° - 25°c (68° - 77°f) [see usp controlled room temperature]. dispense contents in a tight, light-resistant container as defined in the usp. keep out of reach of children. manufactured by: epic pharma, llc laurelton, ny 11413 distributed by: major® pharmaceuticals livonia, mi 48152 refer to package label for distributor's ndc number rev. 11-2018-01 mf503rev11/18 oe1105
Package Label Principal Display Panel:
Package/label display panel ursodiol capsules, usp 300 mg 50 capsules carton label
Package/label display panel ursodiol capsules, usp 300 mg 100 capsules carton label